The role of Cockayne Syndrome group B (CSB) protein in base excision repair and aging

Abstract

Cockayne Syndrome (CS) is a rare human genetic disorder characterized by progressive multisystem degeneration and segmental premature aging. The CS complementation group B (CSB) protein is engaged in transcription coupled and global nucleotide excision repair, base excision repair and general transcription. However, the precise molecular function of the CSB protein is still unclear. In the current review we discuss the involvement of CSB in some of these processes, with focus on the role of CSB in repair of oxidative damage, as deficiencies in the repair of these lesions may be an important aspect of the premature aging phenotype of CS.

The DNA Repair Gene ERCC6 rs1917799 Polymorphism is Associated with Gastric Cancer Risk in Chinese

“…Additionally, its genetic effect on increased GC risk seemed to be enhanced in the context of H pylori infection, smoking and alcohol drinking, although their interaction ERCC6 gene is located at chromosome 10q11.23 of human, encoding a 168 kDa protein (Fousteri et al, 2008). The ERCC6 (CSB) protein has been identified as an indispensable component of transcription coupled repair pathway of NER which is an effective and versatile DNA repair system keeping human genome stability and integrity (Costa et al, 2003;Stevnsner et al, 2008). This protein promotes the production of functional multiprotein complex at the DNA repair site to verify proper synthesis of RNA through interacting with several other essential proteins (Lagerwerf et al, 2011;Sugasawa, 2011).…”

Autophagy and genomic integrity

“…This is of particular interest for human syndromes that arise from genetic deficiency in genes related to DNA repair, such as the premature aging disorder Cockayne Syndrome (CS). 106 In fact, accumulation of dysfunctional mitochondria, mtDNA mutations and oxidatively generated damage were observed in CS type B (CSB) fibroblasts, 107,108 suggesting that the Figure 4 Roles for autophagy in regulating cell fate after DNA damage. We propose that after DNA injury, autophagy can influence cell fate, supporting or impairing cell survival.…”

Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy

“…80% of CS cases are caused by mutations in the group B gene (CSB), with the remaining 20% caused by mutations in CSA. CSB is involved in transcription coupled nucleotide excision DNA repair (TC NER; Anindya et al, 2010) and has been proposed to carry out chro matin remodeling (Citterio et al, 2000), act as a transcription factor (Le May et al, 2010), and function as a co regulator of base excision re pair (BER; Stevnsner et al, 2008).…”

“…This hypersensitivity to UV is a hallmark of CSB deficient cells in culture and is related to the lack of TC NER. However, CSB deficient cells are also sensitive to alkylating and oxidizing agents (Stevnsner et al, 2008) and display defec tive repair of the DNA lesions 8 oxoguanine (Dianov et al, 1999) and 8 hydroxyadenine (Tuo et al, 2002). Oxidative lesions, repaired by BER, are particularly pertinent because the accumulation of oxidized proteins, lipids, and/or nucleic acids have been proposed to be an underlying cause of aging (Balaban et al, 2005).…”